Transcript The Cell, 5e

Section 2 Chemical and Biologic Foundations of Biochemistry
Chapt. 4. Basics of Biochemistry
Student Learning Outcomes:
• Describe the importance of water - solvent of life
• Explain the pH of a solution, and the reason
maintenance of pH, and hydration is so critical
• Describe some strong acids and bases and their
dissociation in water
• Describe some key metabolic acids and bases
• Describe typical buffers in biological systems
• (much more later in Physiology)
4. Homeostasis and maintenance of body pH
Maintenance of body pH is
critical:
• 13-22 mol/day of acid produced
from normal metabolism
• Buffers maintain neutral pH
• CO2 is expired through lungs
• NH4+ and ions are excreted
through kidneys
Fig. 4.1
Water
Water is solvent of life:
• ~ 60% of body is water
• bathes cells
• transports compounds in blood
• separates charged molecules
• dissapates heat
• participates in chemical
reactions
Fig. 4.2 Fluid compartments
in typical 70-kg man
Hydrogen bonds in water
Hydrogen bonds:
• Dipolar nature makes H2O good
solvent; unequal sharing of e• H bonds are weak (5% of covalent)
• Dynamic lattice; thermoregulation
(Sweat cools)
Fig. 4.3
Fig. 4.4:
A. H bonds
B. Hydration shells
around ions
Electrolytes
Table 4.1 Ions in Body Fluids
ECF mmol/L
ICF mmol/L
Cations
Na+
K+
145
4
12
150
Anions
ClHCO3inorganic phosphate
105
25
2
5
12
100
Energy-requiring transporter (Na+/K+ ATPase)
maintains the Na+/K+ gradient
Osmolality and water movement
Water distributes between compartments
• Acccording to osmolality
(concentration of dissolved molecules mOsm/kg H2O)
• Cell membrane semi-permeable
• H2O moves from its high conc to its low
(or from low solute -> high)
Ex. Water from blood to urine
to balance excretion of ions
Ex. Hyperglycemia:
high sugar in blood
pulls water from cells
II. Acids and bases
Review Acids and Bases:
• Acids donate H+ (proton)
• Bases (like OH-) accept H+
Fig. 4.5
pH = -log [H+];
acidic < pH 7; basic > pH 7
in pure H2O, [H+] = 10-7 mol/L = pH of 7
Kd = [H+] [OH-]/ [H2O];
but [H2O] ~ constant
Kw = [H+] [OH-] = 1 x 10-14
increase [H+] -> decrease [OH-],
& vice versa
Table 4 Acids in blood of person
Acid
anion
Sulfuric (H2SO4)
SO42-
pKa
completely
dissociated
source
dietary aa
Carbonic acid
(R-COOH)
R-COO-
3.8
CO2 from TCA
Acetic acid
(R-COOH)
R-COO-
4.76
ethanol metab
Acetoacetic acid
(R-COOH)
R-COO-
3.62
fatty acid oxid
ketone bodies
Ammonium ion
(NH4+)
NH3
9.25
diet N-containing
Acids
Strong acids dissociate completely;
Weak acids dissociate partially – depends on pH
Fig. 4.6:
HA <-> A- + H+
Acid ends in -ic,
Conjugate base
ends in -ate
Ketone bodies
are weak acids
Henderson-Hasselbalch equation
Ka, equilibrium constant for dissociation of weak acid:
describes tendency of HA to donate H+
HA <-> A- + H+
Ka = [H+] [A-] / [HA]
Higher Ka = greater tendency to donate:
acetic acid Ka = 1.74 x 10-5
NH4+ = 5.6 x 10-10
Henderson-Hasselbalch equation
Henderson-Hasselbalch equation describes
relationship between pH of a solution, Ka of acid and
extent of its dissociation
pKa = negative log of Ka
For weak acid HA: pH = pKa + log [A-]/[HA]
a weak acid is 50% dissociated at pH = pKa
[HA] = [A-]
Acids with pKa of 2 are stronger than those pKa of 5:
much more is dissociated at any pH
Buffers resist changes in pH
Buffers resist changes in pH
within ~ 1 pH unit of pKa
Acetic acid:
pH = pKa = 4.76;
50% dissociated:
[A]: [HA] = 1:1
pH 3.76: [A-]: [HA] = 1:10
(not much A- left to
receive more H+)
Fig. 4.7
Metabolic buffers
Buffers maintain body pH in narrow ranges:
despite huge amounts of acid produced/ day
Blood:
pH 7.36-7.44
Intracellular: pH 6.9-7.4
Beating heart: pH 6.8-7.8
Major acid is CO2 from TCA cycle
Metabolic buffers: Bicarbonate-carbonic acid (ECF)
Hemoglobin (rbc), proteins (cells and plasma)
Phosphate in all cell types
Bicarbonate buffer
Bicarbonate is metabolic buffer;
• Acid derived from CO2 produced by
fuel oxidation in TCA cycle
• Reacts to form H2CO3
• Weak acid, dissociates to HCO3• Respiration rate can be adjusted to
modify/ in response to pH of blood
• pH blood = 6.1 + log[HCO3-]/ 0.03 PaCO2
where HCO3- = mEq/ml;
PaCO2 partial pressure arterial blood (mm Hg)
(much more later in Physiology)
Fig. 4.8
Biological buffers maintain pH
Buffering systems in body:
• Bicarbonate and H+ from dissolved CO2 in rbc
• H+ buffered by Hemoglobin (Hb) and PO4-2
• HCO3- in blood buffers H+ from metabolic acids
• Other proteins (Pr) also buffer; e.g., albumin in blood
Fig. 4.9
Urinary hydrogen, ammonium and phosphate
Nonvolatile acid is excreted in urine:
• H+ is often excreted as an undissociated acid
• Urine has pH 5.5 to 7
• Inorganic acids include phosphate, NH4+,
• Organic acids are citric, uric
• Sulfuric acid from S in proteins, other compounds
• NH3 is major buffer (NH3 + H+ <-> NH4+)
NH3 is toxic to neurons;
NH4+ is generated in kidney
Homeostasis requires fluid balance
Fluid balance is critical for
homeostasis:
Dehydration if salt and water
intake < combined rates of
renal and extrarenal loss
Even if fasting, urinary water
dilutes solutes and ions;
expired air loses water.
Hormones help monitor blood
volumes, osmolarity
Key concepts
Key concepts:
• Water is the basis of life – 60% of body – H bonds
•
Intracellular and extracellular (interstitial, blood, lymph)
• Compounds dissolved in water act as acids, bases
•
Acids release H+, bases accept H+
• Homeostasis requires neutral pH ([H+]), proper
amount of body water
• Buffers resist changes of pH if H+ or OH- added:
• Physiological buffers: bicarbonate, phosphate
• Normal metabolism generates acids and CO2
•
CO2 + water -> carbonic acid -> bicarbonate and H+
Clinical comments
Di Abetes: type I diabetes (IDDM) – autoimmune
destruction of b-cells of pancreas
ketoacidosis from blood ketoacids, lowers pH
respiration increases to compensate somewhat
increase urine to dilute blood glucose;
Hyperventilate can give alkalosis in normal person;
Chapt 4. Review questions
Chapter 4 Review questions:
2. Which of the following is a universal property of buffers?
a. buffers are composed of mixture of strong acids and
strong bases
b. buffers work best at pH at which they are completely
dissociated
c. buffers work best at the pH at which they are 50%
dissociated
d. buffers work best at one pH unit lower than the pKa
e. buffers work equally well at all concentrations.
Chapt. 5 Major compounds of the Body
Chapt. 5 Structures of Major Compounds
Student Learning Outcomes:
• Describe structures, functions of major biological
compounds:
• Carbohydrates have C, H, O
• Lipids have fatty acids and glycerol (triglycerides)
• Other lipids are phosphoacyglycerols, cholesterol
• Nitrogen compounds include amino acids,
purines and pyrimidines, nucleosides
Biological compounds
Organic molecules of body have C, H, O, N, S, P:
Carbon is the basis:
• Can do 4 covalent bonds
• Aliphatic
• Aromatic
Naming for number of C,
type of linkage
Fig. 5.1
Functional groups
Functional groups dictate reactivities of molecules –
especially C-O, C-N, C-S bonds
(C- H and C-C less reactive); oxidation state of C important
Fig. 5.2
Reduced vs. oxidized
Reduced and oxidized state of carbon:
Number of electrons around C:
• In Reduction, molecule gains e- and H+;
• In Oxidized state, loses H or gains O
Reduced  oxidized
CH4 most reduced
Acidic and amino groups
Functional groups include:
Fig. 5.3
• Acidic release H+ -> -O• Amine gain H+ -> -NH3+
• unequal sharing
• polar
Fig. 5.5
Fig. 5.4
Reactivities of functional groups
Carboxyl C d+ is very
reactive, attracts d-:
Acid + alcohol = ester
Acid + amine = amide
(like peptide bond)
Phosphate + alcohol =
phosphoester,
(phosphodiester)
Fig. 5.7
Carbohydrates
Carbohydrates: (C H2 O)n
• Nomenclature for C
• Aldehyde vs. ketone
• Polar molecules
• Very soluble in water
• Phosphate makes
• more polar, keeps in cell
Fig. 5.8
Fig. 5.9
Fig. 5.6
Stereoisomers
Asymmetric Carbon:
defines D and L sugars
Stereoisomers of
monosaccharides C6H12O6
Fig. 5.10, 11
Ring forms of sugars in aqueous solution
Sugars form ring structures
in aqueous solution: C=O
reacts with other -OH
Can convert a -> b forms
Enzymes specific for each form
Fig. 5.12, 13
Substituted sugars
Sugars can have substitutions:
-NH2, -PO4,
Oxidized has COOReduced has H, or only OH
Figs. 14, 15
Glycosidic bonds join sugars
Sugars join in glycosidic bonds:
N- or O-linked
a or b –OH of C1
Fig. 5.16
Polysaccharides (Cooper cell biol)
Glycogen: storage in
animal cells
Starch: storage in plant
cells
Cellulose plant cell wall.
glucose, β configuration.
β(1→4) linkages form ->
long chains that pack to
form fibers
Lipids
Lipids have 3 main roles:
– Energy storage
– Major components
of cell membranes
– Important in cell signaling:
steroid hormones, messenger molecules
Fatty acids
Fatty acids are simplest lipids: long hydrocarbon
chains (16 or 20 C) with (COO−) at one end.
Hydrocarbon chain is hydrophobic
Saturated fatty acids:
no double bonds.
Unsaturated fatty acids:
one or more
double bonds
(kink structure)
Fig. 5.1 Cooper Cell Biology
Fatty acids
Fatty acids are
saturated (solid)
or unsaturated
(fluid)
Nomenclature:
Cis- (natural) vs
trans- from
artificial
hydrogenation of
polyunsat f.a.
Fig. 5.17
Fats – acyglycerols
Fats = triacylglycerols =
triglycerides: 3 fatty acids, glycerol
Phosphoacylglycerols =
2 fatty acids, glycerol, PO4Fig. 5.18
Fig. 5.19
sphingolipids
Sphingolipids = serine + 2 fatty acids
Sphingosine = serine + palmitate
Ceramide = fatty acid + sphingosine
Gangliosides = sugar + sphingolipid
Sphingomyelin:
component of
cell membranes,
myelin sheath
Fig. 5.20
Steroids cholesterol
Steroids have 4 ring structure:
• Not very water soluble
Cholesterol is precursor for others:
Sex hormones
Bile salt cholic acid is soluble
Fig. 5.21
Amino acids
Amino acids have –NH2
-COOH
Humans only La-aa in proteins (Fig. 5.22)
(Bacteria have D-aa in cell walls)
Fig. 5.22
neurotransmitter
Nitrogen bases
Nitrogen-containing ring structures
(heterocyclic rings, nitrogenous bases):
N on ring can form H bonds with other molecules
Purines:
A and G
Pyrimidines: T, C and U
Pyridines: - vitamins nicotinic acid (niacin)
pyridoxine (vitamin B6)
Fig. 5.23
nucleosides
• Bases are linked to sugars form nucleosides.
• DNA has sugar 2′-deoxyribose, RNA has ribose.
• Nucleotides have one or more phosphate groups
linked to 5′ carbon of sugars.
Cooper Cell Biology
The Molecules of Cells
Important nucleotides: adenosine 5′-triphosphate
(ATP), principal form of chemical energy
Some (e.g., cyclic AMP) act as signaling molecules
within cells.
ATP
Compare dATP to ATP
cAMP
Tautomers
Tautomers in N-containing rings are alternate forms,
can have different properties, reactivities:
Ex. Uric acid forms Na-urate crystals in gout
Acidic urine can precipitate uric acid (kidney stone)
Fig. 5.24
Key concepts
Key concepts:
Carbohydrates [sugars, (CH2O)n];
asymmetric carbon, carbonyl, linkages of sugars
Lipids are not very water soluble (hydrophobic):
triacylglcerol, phosphoacylglycerol, cholesterol
Nitrogen-containing compounds:
amino acids, purines, pyrimidines, pyridines
nucleosides, nucleotides
Glycoproteins and proteoglycans - sugars and proteins
Clinical comments
Lotta Topaigne – gouty arthritis:
urate from breakdown of G and A, precipitates with Na+
phagocytosed by white blood cells; inflammatory reaction
Di Abietes – diabetic detoacidosis (DKA)
measure blood glucose, ketone bodies
Figure 2.33 A protein interaction map of Drosophila melanogaster
Review questions:
• Diagram the structure of a phospholipid and a fat
• What are the major functions of fats and
phospholipids in cells?
• Diagram the structure of D-glucose, ribose and
dexoyribose in ring form
• Diagram the structure of a disaccharide